Science in Focus: Daniel Burden

Instant Messaging

Imagine that your cell phone rings on a cold November evening. The voice on the other end sounds distorted, and a bit panicked. "There's been a car accident just down the street. Your young son is involved. He is injured and crying near the roadside."

Immediately, you experience a flood of emotions. You rush for a flashlight and head out into the night as your heart begins to pound. As you don a jacket, you notice that your body is shaking. You hear sounds of emergency vehicles arriving at the scene. Nerve impulses race up and down your body as the noise and lights of the accident intensify. You sprint to find your injured loved one.

Amazingly, this altogether human response is facilitated by inanimate molecular signals that cause the body's cells to productively interact. The interaction arises from specialized molecular switches, called receptors, which pass messages through the outer cell membrane into the interior of cells. Inside, molecular machinery responds by producing chemicals that equip your body for this heightened moment of stress.

This year's Nobel Prize in Chemistry was awarded to Robert J. Lefkowikz of Duke University Medical Center and Brian K. Kobilik of Stanford University's School of Medicine for their groundbreaking work on a particular class of switches called G-protein coupled receptors (GPCRs). These message-passing molecules are ubiquitous and can pick up signals from a variety of sources, including photons, odors, neurotransmitters, and hormones.

Remarkably, all GPCRs have similar molecular structure and mechanical action. Embedded in the cellular membrane by a characteristic seven transmembrane segments, these protein switches are activated when messenger molecules, such as adrenalin, cortisol, and noradrenalin, arrive at the outside of a cell and bind to the receptor. This causes a shape-change at the other end of the protein residing inside the cell. Another class of molecules, called G-proteins, recognizes this change and begins a signaling cascade that springs subcellular mechanisms into action—actions that eventually cause the heart to pound, the lungs to inflate, muscles to contract, and the body to take flight. So crucial is this communication fulcrum to human well-being that nearly 50 percent of all medications on the market today, responding to a wide array of maladies, target GPCRs.

Lefkowicz began his work over 40 years ago, contributing a number of significant advances in the field, including (in 1970) the first direct detection and visualization of ligand-gated receptors on a cell membrane. In 2011, his colleague and former understudy, Kobilik, contributed what is now considered a crowning achievement: an image, produced by x-ray crystallography, of a GPCR caught in the act of message transmission.

But it is not only Nobel Prize-winning scientists who have made this year's headlines in biomembrane science. Entrepreneurs and technologists have made news of their own.

Another class of molecules, called ion channels, operates by forming tiny holes in the outer membrane of cells. These open conduits allow ions and molecules to cross the membrane barrier. As a result, some channels are classified as toxins because they enable a flood of foreign material to enter the cell and upset the delicate biochemical balance, to the point of cell death.

Over the past decade, investigators have been attempting to use these toxins as an innovative tool for DNA sequencing. In a completely anthropogenic application, a strand of DNA is forced through an open pore, like tape in a ticker-tape reader. During DNA's passage, engineered sites within the pore enable genetic sequence information to be acquired with potentially stunning speed and duration. This year a British company developing the approach (Oxford Nanopore) announced a record-breaking read length of 48 thousand bases, a feat many thought would not be possible.

Continued advancement in DNA sequencing will create inexpensive and rapid genomic sequencing for everyone. One day this could lead to a more personalized approach to medicine. Such technology will also intensify societal and ethical debates over the risks and rewards of ubiquitous human genetic information.

Membrane bioscience has had a groundbreaking year, indeed. But, it will continue to captivate the energies of scientists and technologists for many years to come.

Daniel Burden is professor of chemistry with a research program in biomembrane dynamics at Wheaton College.